Treatment Encouraging in Mouse Model for Prostate Cancer

A new drug helped prevent prostate cancer in mice and also decreased the cancer's spread to the lymph nodes and lungs.

Scientists at Baylor College of Medicine developed the highly specialized mouse model for the study, which is published in the April 15 issue of the journal Cancer Research. They collaborated with researchers at Encore Pharmaceuticals in Loma Linda, Calif., and Loma Linda University.

"What makes our mouse model unique is that it is the first of its kind that specifically and spontaneously develops metastatic prostate cancer," says Dr. Norman Greenberg, Baylor associate professor of molecular and cellular biology and urology and senior author of the paper.

The Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model was genetically engineered so that each mouse will develop its own prostate cancer. Many other mouse models use prostate cancer cells from tumors that have already formed. Those cells are grafted onto the prostate to produce disease, which precludes prevention studies.

"The progression of the disease in TRAMP closely mimics what is seen in humans and provides an ideal way to test strategies for prevention, intervention and regression," Dr. Greenberg says. "The TRAMP mouse gives us important clues as to what we might expect to happen in humans, so it should help us narrow the possibilities."

Although the TRAMP model takes a little longer to use than some of the graft models, "the authentic and spontaneous features of the model outweigh those concerns," Dr. Greenberg says. "And it is still a lot faster and cheaper than running clinical trials."

The study evaluated the effect of a non-steroidal anti-inflammatory drug, known as E-7869 or R-flurbiprofen, in 60 TRAMP mice on two types of diets: high-fat and low-fat.

Nearly 50 percent of the tissue in mice on a high-fat diet that did not receive the drug showed evidence of cancer during the study. But only 29 percent of the tissue in mice given a high dose of E-7869 developed tumors, and only 44 percent in mice given a low dose of the drug developed tumors.

Nearly 60 percent of the tissue showed signs of cancer in mice on a low-fat diet that did not receive the drug, but only 21 percent of tissue had tumors in mice given a high dose of E-7869. A low dose was not given to the mice on low-fat diets.

"Because our mouse model contains genetic instructions to develop aggressive prostate tumors, E-7869's ability to prevent cancer is highly encouraging," Dr. Greenberg says. "But we were also impressed by E-7869's impact on the spread of cancer."

Lymph nodes and lungs were checked for signs that the prostate cancer had metastasized, or spread.

Forty percent of tissue in lymph nodes and lungs showed signs of cancer in mice on a high-fat diet that did not receive E-7869. Forty-two percent of this tissue in mice that received a low dose of the drug had evidence of cancer. But only 6 percent of this tissue had cancer in mice that were given a high dose.

Ten percent of the tissue in lymph nodes and lungs had cancer in the low-fat mice that did not receive the drug, but no cancer was detected in this tissue in mice given a high dose of E-7869.

"Our results in mice suggest that E-7869 could be a promising drug for preventing and treating the second leading cause of cancer death among men in the United States, but human clinical trials will now have to prove that," Dr. Greenberg says.

Dr. Roberto Barrios, a Baylor associate professor of pathology, is a co-author of the paper.

The study was funded by a Specialized Program of Research Excellence grant to Baylor from the National Cancer Institute, with additional support from Adventist Health Systems Loma Linda and CaPCURE.

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©2006 Texas Medical Center

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